5H-1,3,4-thiadiazolo(3,2-A)pyrimidin-5-one derivatives and functional compositions containing the same

ABSTRACT

A class of novel 5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one derivatives are disclosed. These compounds exhibit remarkable fungicidal activities for pathogenic fungi of cucumber gray mold, cucumber downy mildew. Alternaria sooty spot of Chinese mustard, apple Alternaria leaf spot, pear black spot, rice blast, tomato late blight, etc.

This application is a continuation of application Ser. No. 07/027,250,filed on Mar. 18, 1987, now abandoned.

FIELD OF THE INVENTION

This invention relates to a novel agricultural-horticultural fungicide.More particularly, this invention relates to a class of novel5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one derivatives and fungicidalcompositions containing the same.

BACKGROUND OF THE INVENTION

In the specification of Japanese Laying-Open Patent Publication No.52-118494 (1977), it is described that a thiadiazolo[3,2-a]pyrimidinonederivative represented by the general formula ##STR1## wherein R¹ standsfor an alkyl group or an aryl group; R² stands for a hydrogen atom, ahalogen atom, a nitro group, a carboalkoxy group or an alkyl group; R³stands for an alkyl group or an aralkyl group; and Y stands for --SO--or --SO₂ --, exhibits an activity inhibiting proliferation of cancercells and is useful as an anticancer agent.

In the specification of Japanese Laying-Open Patent Publication No.58-177997 (1983), it is described that a thiadiazolopyrimidinonederivative represented by the general formula ##STR2## wherein R¹ standsfor a 1 or 2H-tetrazol-5-yl group, a carboxy group or a loweralkoxycarbonyl group; R² stands for an aryl group or a heteroaryl groupwhich may be substituted with an alkyl group, an alkoxy group, a hydroxygroup or a halogen atom; X stands for an alkylene group, an alkenylenegroup, an alkynylene group or any of the above groups, to an end ofwhich an oxygen atom, a sulfur atom or SO₂ is attached; wherein each ofthe groups represented by X may be substituted with one or more linearor cyclic alkyl groups or with the substituent R², and a physiologicallyacceptable salt thereof have excellent antiallergic activity.

As described above, there were known several thiadiazolopyrimidinonederivatives, which have a chemical structure similar to that of thecompounds of the present invention. However, these are medicinals, andthey do not clearly exhibit activities as pesticides.

We paid attention to the 5H-1,3,4-thiadiazolo[3,2-a]pyrimidin structure,which is the skeleton of many substances used as medicines, and wesynthesized a number of derivatives thereof and studied their biologicalactivities. As a result, we found that some specific compounds havingthe 5H-1,3,4-thiadiazolo[3,2-a]pyrimidin structure exhibit an excellentproperty as an agricultural-horticultural pesticide, and completed thisinvention.

That is to say, the object of this invention is to provide novel5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one derivatives, usefulagricultural-horticultural fungicidal compositions containing saidderivatives, a process for preparing said derivatives as well as a classof novel compounds, which are the starting materials for preparation ofsaid derivatives.

DISCLOSURE OF THE INVENTION

This invention provides a 5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onederivative represented by the general formula (I) ##STR3## wherein Xstands for a hydrogen atom, a halogen atom, a linear or branched loweralkyl group, a lower alkoxy group, a lower acyl group, atrihalo-lower-alkoxy group, a lower alkynyl group, a phenyl group, acyano group, a phenoxy group or a nitro group;

Y stands for a hydrogen atom, a halogen atom, a linear or branched loweralkyl group, a halo-lower-alkyl group, a lower alkoxy group, a loweralkynyl group, a phenyl-lower-alkynyl group, a lower-alkyl-amino group,or a cyano group; and

R stands for a linear or branched alkyl group, a cyclohexyl-lower-alkylgroup, a lower alkenyl group, a cyclohexyl group, a phenoxy-lower-alkylgroup, a halo-alkyl group, a halo-alkenyl group, alower-alkoxycarbonyl-lower-alkyl group, atri-lower-alkyl-silyl-lower-alkyl group, a phenyl-lower-alkyl group, analkoxy-lower-alkyl group, a phenyl group which may be substituted withone or more halogen atoms, lower alkyl groups or nitro groups or loweralkoxy groups; a group represented by the general formula ##STR4##wherein Z stands for a halogen atom, a lower alkyl group, a lower alkoxygroup, a trihalo-lower-alkyl group or a nitro group, and n is an integerof 1 or 2, wherein the two substituents may be the same or different;

with a proviso that when X is a hydrogen atom, a halogen atom, a nitrogroup, or an alkyl group and that Y is an alkyl group, R is not an alkylgroup nor a phenyl-lower-alkyl group.

Further this invention provides a process for preparing a5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one derivative represented by thegeneral formula (I) ##STR5## wherein X stands for a hydrogen atom, ahalogen atom, a linear or branched lower alkyl group, a lower alkoxygroup, a lower acyl group, a trihalo-lower-alkoxy group, a lower alkynylgroup, a phenyl group, a cyano group, a phenoxy group or a nitro group;

Y stands for a hydrogen atom, a halogen atom, a linear or branched loweralkyl group, a halo-lower-alkyl group, a lower alkoxy group, a loweralkynyl group, a phenyl-lower-alkynyl group, a lower-alkyl-amino group,or a cyano group; and

R stands for a linear or branched alkyl group, a cyclohexyl-lower-alkylgroup, a lower alkenyl group, a cyclohexyl group, a phenoxy-lower-alkylgroup, a halo-alkyl group, a halo-alkenyl group, alower-alkoxycarbonyl-lower-alkyl group, atri-lower-alkyl-silyl-lower-alkyl group, a phenyl-lower-alkyl group, analkoxy-lower-alkyl group, a phenyl group which may be substituted withone or more halogen atoms, lower alkyl groups or nitro groups or loweralkoxy groups; a group represented by the general formula ##STR6##wherein Z stands for a halogen atom, a lower alkyl group, a lower alkoxygroup, a trihalo-lower-alkyl group or a nitro group, and n is an integerof 1 or 2, wherein the two substituents may be the same or different;

with a proviso that when X is a hydrogen atom, a halogen atom, a nitrogroup, or an alkyl group and that Y is an alkyl group, R is not an alkylgroup nor a phenyl-lower-alkyl group,

comprising oxidizing a compound represented by the general formula (II)##STR7## wherein X, Y and R are as defined above by a procedure knownper se.

Still further, this invention provides a5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one derivative represented by thegeneral formula (II) ##STR8## wherein X stands for a hydrogen atom, ahalogen atom, a linear or branched lower alkyl group, a lower alkoxygroup, a lower acyl group, a trihalo-lower-alkoxy group, a lower alkynylgroup, a phenyl group, a cyano group, a phenoxy group or a nitro group;

Y stands for a hydrogen atom, a halogen atom, a linear or branched loweralkyl group, a halo-lower-alkyl group, a lower alkoxy group, a loweralkynyl group, a phenyl-lower-alkynyl group, a lower-alkyl-amino group,or a cyano group; and

R stands for a linear or branched alkyl group, a cyclohexyl-lower-alkylgroup, a lower alkenyl group, a cyclohexyl group, a phenoxy-lower-alkylgroup, a halo-alkyl group, a halo-alkenyl group, alower-alkoxycarbonyl-lower-alkyl group, atri-lower-alkyl-silyl-lower-alkyl group, a phenyl-lower-alkyl group, analkoxy-lower-alkyl group, a phenyl group which may be substituted withone or more halogen atoms, lower alkyl groups or nitro groups or loweralkoxy groups; a group represented by the general formula ##STR9##wherein Z stands for a halogen atom, a lower alkyl group, a lower alkoxygroup, a trihalo-lower-alkyl group or a nitro group, and n is an integerof 1 or 2, wherein the two substituents may be the same or different;

with a proviso that when X is a hydrogen atom, a halogen atom, a nitrogroup, or an alkyl group and that Y is an alkyl group, R is not an alkylgroup nor a phenyl-lower-alkyl group.

Still further, this invention provides an agricultural-horticulturalfungicide composition comprising a5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one derivative represented by thegeneral formula (I) ##STR10## wherein X stands for a hydrogen atom, ahalogen atom, a linear or branched lower alkyl group, a lower alkoxygroup, a lower acyl group, a trihalo-lower-alkoxy group, a lower alkynylgroup, a phenyl group, a cyano group, a phenoxy group or a nitro group;

Y stands for a hydrogen atom, a halogen atom, a linear or branched loweralkyl group, a halo-lower-alkyl group, a lower alkoxy group, a loweralkynyl group, a phenyl-lower-alkynyl group, a lower-alkyl-amino group,or a cyano group; and

R stands for a linear or branched alkyl group, a cyclohexyl-lower-alkylgroup, a lower alkenyl group, a cyclohexyl group, a phenoxy-lower-alkylgroup, a halo-alkyl group, a halo-alkenyl group, alower-alkoxycarbonyl-lower-alkyl group, atri-lower-alkyl-silyl-lower-alkyl group, a phenyl-lower-alkyl group, analkoxy-lower-alkyl group, a phenyl group which may be substituted withone or more halogen atoms, lower alkyl groups or nitro groups or loweralkoxy groups; a group represented by the general formula ##STR11##wherein Z stands for a halogen atom, a lower alkyl group, a lower alkoxygroup, a trihalo-lower-alkyl group or a nitro group, and n is an integerof 1 or 2, wherein the two substituents may be the same or different;

with a proviso that when X is a hydrogen atom, a halogen atom, a nitrogroup, or an alkyl group and that Y is an alkyl group, R is not an alkylgroup nor a phenyl-lower-alkyl group,

and an agricultural-horticulturally acceptable carrier.

Of the compounds of the general formula (I), preferred are those ofwhich X stands for a hydrogen atom, a halogen atom, a C₁₋₄ -alkyl group,a C₁₋₃ -alkoxy group, an ethynyl group, an acetyl group, atrifluoroethoxy group, a phenyl group, a phenoxy group, a nitro group ora cyano group; Y stands for a hydrogen atom, a halogen atom, a C₁₋₃-alkyl group, a C₁₋₂ -alkoxy group, a C₂₋₃ -alkynyl group, achloromethyl group, a phenyl-ethynyl group, a C₂₋₃ -alkylamino group ora cyano group; and R stands for a C₁₋₉ -alkyl group, a cyclohexylmethylgroup, an allyl group, a C₂₋₃ -alkynyl group, a cyclohexyl group, aphenoxyalkyl group, a haloalkyl group, a dichloroalkenyl group, anethoxycarbonylbutyl group, an alkoxyalkyl group, a phenyl-C₁₋₄ -alkylgroup, a trimethylsilylpropyl group, a phenyl group which may besubstituted with a halogen atom, one C₁₋₄ -alkyl group, a C₁₋₃ -alkoxygroup, a nitro group; a group represented by the general formula##STR12## wherein Z stands for a halogen atom, a C₁₋₄ -alkyl group, aC₁₋₃ -alkoxy group, a trifluoromethyl group or a nitro group.

Examples of the compounds of the present invention represented by thegeneral formula (I) are listed in Table 1. Each compound is hereinafterreferred to by the compound number given in the table.

                                      TABLE 1                                     __________________________________________________________________________     ##STR13##                                                                    Compound No.                                                                          X       Y         R            m.p. (°C.)                      __________________________________________________________________________    1       H       CH.sub.3                                                                                 ##STR14##   157˜162                          2       "       "                                                                                        ##STR15##   192˜194                          3       "       "                                                                                        ##STR16##   212˜216                          4       "       "                                                                                        ##STR17##   210˜213                          5       "       "                                                                                        ##STR18##   209˜211                          6       "       "                                                                                        ##STR19##   164˜168                          7       "       "                                                                                        ##STR20##   179˜182                          8       "       "                                                                                        ##STR21##   156˜160                          9       "       "                                                                                        ##STR22##   175.5˜179                        10      "       "                                                                                        ##STR23##   114˜116                          11      "       "                                                                                        ##STR24##   95˜98                            12      H       CH.sub.3                                                                                 ##STR25##   150˜152                          13      "       "                                                                                        ##STR26##   185˜187                          14      "       "                                                                                        ##STR27##   104˜106                          15      "       "                                                                                        ##STR28##   208˜210                          16      "       "                                                                                        ##STR29##   231˜234                          17      "       "                                                                                        ##STR30##   149˜152                          18      CH.sub.3                                                                              H                                                                                        ##STR31##   190˜193                          19      "       "                                                                                        ##STR32##   209˜210                          20      "       "                                                                                        ##STR33##   162˜164                          21      H       "         n-C.sub.6 H.sub.13                                                                         65˜67                            22      "       "         n-C.sub.7 H.sub.15                                                                         88˜90                            23      CH.sub.3                                                                              "         n-C.sub.5 H.sub.11                                                                         107˜109                          24      "       "         n-C.sub.6 H.sub.13                                                                         79˜81                            25      "       "         n-C.sub.7 H.sub.15                                                                         90˜92                            26      CH.sub.3                                                                              H         n-C.sub.8 H.sub.17                                                                         96˜98                            27      "       "                                                                                        ##STR34##   124˜128                          28      C.sub.2 H.sub.5                                                                       "         n-C.sub.7 H.sub.15                                                                         78˜80                            29      i-C.sub.3 H.sub.7                                                                     "         n-C.sub.7 H.sub.15                                                                         59˜62                            30      H       Cl        n-C.sub.7 H.sub.15                                                                         104˜110                          31      "       F         n-C.sub.7 H.sub.15                                                                         115˜117                          32      CH.sub.3                                                                              Cl        n-C.sub.7 H.sub.15                                                                         136˜138                          33      "       F         n-C.sub.7 H.sub.15                                                                         143˜146                          34      H       CH.sub.3                                                                                 ##STR35##   191˜194                          35      "       "                                                                                        ##STR36##   140˜143                          36      "       "                                                                                        ##STR37##   209˜215                          37      "       "                                                                                        ##STR38##   207˜208                          38      "       "                                                                                        ##STR39##   186˜188                          39      "       "                                                                                        ##STR40##   214˜216                          40      CH.sub.3                                                                              H                                                                                        ##STR41##   198˜200                          41      "       "                                                                                        ##STR42##   156˜158                          42      H       "                                                                                        ##STR43##   135˜138                          43      "       "                                                                                        ##STR44##   179˜188                          44      CH.sub.3                                                                              "                                                                                        ##STR45##   183˜186                          45      "       "                                                                                        ##STR46##   191˜193                          46      "       "                                                                                        ##STR47##   200˜203                          47      "       "                                                                                        ##STR48##   199˜204                          48      "       "                                                                                        ##STR49##   183˜185                          49      "       "                                                                                        ##STR50##   205˜208                          50      "       "                                                                                        ##STR51##   178˜180                          51      "       "         n-C.sub.3 H.sub.7                                                                          149˜151                          52      "       "         n-C.sub.4 H.sub.9                                                                          107.5˜109                        53      C.sub.2 H.sub.5                                                                       "                                                                                        ##STR52##   67˜77                            54      C.sub.2 H.sub.5                                                                       H         n-C.sub.6 H.sub.13                                                                         67˜69                            55      i-C.sub.3 H.sub.7                                                                     "                                                                                        ##STR53##     162˜163.5                      56      "       "                                                                                        ##STR54##   141˜146                          57      "       "                                                                                        ##STR55##   135˜138                          58      "       "         n-C.sub.4 H.sub.9                                                                          105˜106                          59      "       "         n-C.sub.5 H.sub.11                                                                         108˜109                          60      "       "         n-C.sub.6 H.sub.13                                                                         75˜76                            61      i-C.sub.4 H.sub.9                                                                     "                                                                                        ##STR56##   115˜121                          62      "       "                                                                                        ##STR57##   134˜138                          63      "       "                                                                                        ##STR58##   155˜158                          64      "       "         n-C.sub.4 H.sub.9                                                                          84˜87                            65      H       "                                                                                        ##STR59##   206˜208                          66      "       n-C.sub.3 H.sub.7                                                                        ##STR60##   163˜165                          67      "       "                                                                                        ##STR61##   216˜218                          68      H       n-C.sub.3 H.sub.7                                                                        ##STR62##   139˜141                          69      i-C.sub.4 H.sub.9                                                                     Cl        n-C.sub.4 H.sub.9                                                                          140˜142                          70      "       "         n-C.sub.6 H.sub.13                                                                         118˜121                          71      "       F         n-C.sub.5 H.sub.11                                                                         127˜130                          72      "       "         n-C.sub.6 H.sub.13                                                                         107˜108                          73      CH.sub.3                                                                              CH.sub.3                                                                                 ##STR63##   195˜197                          74      "       Cl                                                                                       ##STR64##   258˜261                          75      "       "         n-C.sub.3 H.sub.7                                                                          196˜197                          76      "       "         n-C.sub.4 H.sub.9                                                                          151˜153                          77      "       "         n-C.sub.5 H.sub.11                                                                         156˜157                          78      "       "         n-C.sub.6 H.sub.13                                                                         135˜139                          79      "       F         n-C.sub.4 H.sub.9                                                                          131˜132                          80      "       "         n-C.sub.5 H.sub.11                                                                         128˜132                          81      "       "         n-C.sub.6 H.sub.13                                                                         143˜145                          82                                                                                     ##STR65##                                                                            H                                                                                        ##STR66##   186˜190                          83      "       "                                                                                        ##STR67##   201˜203                          84      "       "         n-C.sub.4 H.sub.9                                                                           96˜100                          85      "       "         n-C.sub.6 H.sub.13                                                                         94˜95                            86      CCH     "         "            165˜175                          87      "       "         n-C.sub.7 H.sub.15                                                                         180˜182                          88      OCH.sub.3                                                                             "                                                                                        ##STR68##   170˜172                          89      "       "                                                                                        ##STR69##   112˜115                          90      "       "                                                                                        ##STR70##   151˜153                          91      "       "                                                                                        ##STR71##   194˜196                          92      "       "                                                                                        ##STR72##   166˜175                          93      "       "         n-C.sub.6 H.sub.13                                                                         110˜111                          94      "       "         n-C.sub.7 H.sub.15                                                                         106˜109                          95      "       "         n-C.sub.9 H.sub.19                                                                           104˜105.5                                                             refractive index                                                              (.sub.n D.sup.20)                      96      OC.sub.2 H.sub.5                                                                      "                                                                                        ##STR73##   184˜187                          97      "       "         n-C.sub.6 H.sub.13                                                                         72˜75                            98                                                                                     ##STR74##                                                                            "                                                                                        ##STR75##   148˜153                          99      "       "                                                                                        ##STR76##   201˜205                          100     "       "         n-C.sub.4 H.sub.9                                                                          133˜135                          101     "       "         n-C.sub.6 H.sub.13                                                                         97˜99                            102     Cl      "                                                                                        ##STR77##   209˜213                          103     "       "         n-C.sub.5 H.sub.11                                                                         140˜142                          104     "       "         n-C.sub.6 H.sub.13                                                                         142˜143                          105     "       "         n-C.sub.7 H.sub.15                                                                         145˜147                          106     "       "         n-C.sub.8 H.sub.17                                                                         146˜148                          107     "       "                                                                                        ##STR78##   .sub.n D.sup.20 1.5785                 108     F       "                                                                                        ##STR79##   225˜228                          109     "       "                                                                                        ##STR80##   190˜191                          110     F       H         n-C.sub.6 H.sub.13                                                                         75˜76                            111     Br      "         n-C.sub.7 H.sub.15                                                                         136˜140                          112     NO.sub.2                                                                              NHC.sub.3 H.sub.7 -i                                                                    n-C.sub.7 H.sub.15                                                                         124˜125                          113     H       C CH      n-C.sub.6 H.sub.13                                                                         152˜155                          114     "       "         n-C.sub.7 H.sub.15                                                                         146˜149                          115     "       CCCH.sub.3                                                                              n-C.sub.6 H.sub.13                                                                         122˜125                          116     "       "         n-C.sub.7 H.sub.15                                                                         127˜129                          117     "       CH.sub.2 Cl                                                                              ##STR81##   194˜198                          118     "       "         n-C.sub.7 H.sub.15                                                                         95˜97                            119     Cl      Cl        n-C.sub.5 H.sub.11                                                                         207˜209                          120     "       "         n-C.sub.6 H.sub.13                                                                         194˜198                          121     "       F         "            185˜188                          122     CH.sub.3                                                                              H                                                                                        ##STR82##   186˜188                          123     H       CH.sub.3                                                                                 ##STR83##   146˜150                          124     H       CH.sub.3  CH.sub.2 CHCH.sub.2                                                                        133˜135                          125     "       "                                                                                        ##STR84##   156˜158                          126     "       "         (CH.sub.2).sub.4 CO.sub.2 C.sub.2 H.sub.5                                                  138˜140                          127     "       "         (CH.sub.2).sub.6 Cl                                                                        126˜128                          128     "       "         (CH.sub.2).sub.3 CHCCl.sub.2                                                               106˜108                          129     Cl      H                                                                                        ##STR85##   197˜203                          130     H       "                                                                                        ##STR86##   191˜194                          131     OCH.sub.2 CF.sub.3                                                                    "                                                                                        ##STR87##   160˜164                          132     F       "                                                                                        ##STR88##   191˜194                          133     H       "                                                                                        ##STR89##   175˜176                          134     "       "                                                                                        ##STR90##   113˜117                          135     "       "                                                                                        ##STR91##   175˜177                          136     OC.sub.3 H.sub. 7                                                                     "                                                                                        ##STR92##   144˜147                          137     H       "                                                                                        ##STR93##   163˜165                          138     H       H                                                                                        ##STR94##   210˜213                          139     "       "                                                                                        ##STR95##     160˜161.5                      140     "       "                                                                                        ##STR96##   142˜145                          141     Cl      "                                                                                        ##STR97##   233˜235                          142     "       "                                                                                        ##STR98##   201˜203                          143     "       "                                                                                        ##STR99##   193˜197                          144     H       C.sub.2 H.sub.5                                                                          ##STR100##  159˜163                          145     OC.sub.2 H.sub.5                                                                      H                                                                                        ##STR101##  182˜185                          146     Cl      CH.sub.3                                                                                 ##STR102##  217˜221                          147     OCH.sub.3                                                                             H                                                                                        ##STR103##  154˜155                          148     "       "                                                                                        ##STR104##  184˜185                          149     "       "                                                                                        ##STR105##  179˜180                          150     F       "                                                                                        ##STR106##  231˜233                          151     H       "                                                                                        ##STR107##  176˜179                          152     F       CH.sub.3                                                                                 ##STR108##  218˜219                          153     H       C.sub.2 H.sub.5                                                                          ##STR109##  155˜158                          154     CH.sub.3                                                                              CH.sub. 3                                                                                ##STR110##  223˜227                          155     F       H                                                                                        ##STR111##  199˜201                          156     Cl      CH.sub.3                                                                                 ##STR112##  266˜269                          157     "       H                                                                                        ##STR113##  264˜267                          158     F       "                                                                                        ##STR114##  215˜218                          159     OCH.sub.3                                                                             "                                                                                        ##STR115##  167˜169                          160     H       C.sub.2 H.sub.5                                                                          ##STR116##  140˜142                          161     F       CH.sub.3                                                                                 ##STR117##  237.5˜238.5                      162     Cl      H         n-C.sub.9 H.sub.19                                                                         146˜148                          163     NO.sub.2                                                                              Cl        n-C.sub.6 H.sub.13                                                                         182˜185                          164     H       CN        n-C.sub.6 H.sub.13                                                                         144˜146                          165     "                                                                                      ##STR118##                                                                             n-C.sub.6 H.sub.13                                                                         134˜137                          166     H                                                                                      ##STR119##                                                                             n-C.sub.7 H.sub.15                                                                         127˜129                          167     "       CN        n-C.sub.7 H.sub.15                                                                         114˜119                          168     F       H         n-C.sub.7 H.sub.15                                                                           92˜93.5                        169     "       "         n-C.sub.8 H.sub.17                                                                         71˜77                            170     NO.sub.2                                                                              I         n-C.sub.6 H.sub.13                                                                         159˜161                          171     H       CH.sub.3                                                                                 ##STR120##  150˜152                          172     "       "         (CH.sub.2).sub.2 OC.sub.6 H.sub.13                                                         48˜54                            173     "       "                                                                                        ##STR121##  198˜201                          174     CN      H         n-C.sub.6 H.sub.13                                                                         146˜150                          175     NO.sub.2                                                                              OC.sub.2 H.sub.5                                                                        n-C.sub.6 H.sub.13                                                                         134˜136                          176     "       OCH.sub.3 n-C.sub.6 H.sub.13                                                                         150˜152                          177     Cl      CCH       n-C.sub.6 H.sub.13                                                                         150˜153                          178     "       CN        n-C.sub.6 H.sub.13                                                                         171˜174                          179     NO.sub.2                                                                              NHC.sub.2 H.sub.5                                                                       n-C.sub.6 H.sub.13                                                                         144˜146                          180     COCH.sub.3                                                                            H         n-C.sub.6 H.sub.13                                                                         124˜125                          181     H       CH.sub.2 Cl                                                                             n-C.sub.6 H.sub.13                                                                         69˜70                            182     Cl      "         n-C.sub.6 H.sub.13                                                                         122˜124                          183     OCH.sub.3                                                                             H         n-C.sub.8 H.sub.17                                                                         109˜110                          184     Cl      "         CH.sub.3     225˜228                          185     "       "         CH.sub.2 CF.sub.3                                                                          187˜190                          186     "       "                                                                                        ##STR122##  178˜181                          187     "       "         CH.sub.2 CH(C.sub.2 H.sub.5).sub.2                                                           106˜107.5                      188     NO.sub.2                                                                              Cl        n-C.sub.7 H.sub.15                                                                         173˜176                          189     "       OCH.sub.3 n-C.sub.7 H.sub.15                                                                           153˜154.5                      190     COCH.sub.3                                                                            H         n-C.sub.7 H.sub.15                                                                         131.5˜133.5                      191     CN      "         n-C.sub.7 H.sub.15                                                                         130˜132                          192     "       "         n-C.sub.8 H.sub.17                                                                         122˜124                          193     "       CH.sub.3  n-C.sub.7 H.sub.15                                                                         172˜175                                                                 refractive index                                                              (.sub.n D.sup.20)                      194     OCH.sub.3                                                                             H         CH.sub.2 CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9                                                .sub.n D.sup.20 1.5612                 195     Cl      "         (CH.sub.2).sub.3 C.sub.3 H.sub.7 -i                                                        151˜153                          196     "       "         (CH.sub.2).sub.2 CH(CH.sub.3 )C.sub.2 H.sub.5                                              130˜132                          197     "       "         CH.sub.2 CH(CH.sub.3)C.sub.3 H.sub.7 -n                                                    125˜127                          198     OCH.sub.3                                                                             "         (CH.sub.2).sub.3 Si(CH.sub.3).sub.3                                                        112˜114                          199     H       CH.sub.3  (CH.sub.2).sub.3 Si(CH.sub.3).sub.3                                                        155˜157                          200     CN      F         n-C.sub.7 H.sub.15                                                                         165˜167                          201     CH.sub.3                                                                              CN        n-C.sub.6 H.sub.13                                                                         134˜135                          202     CN      H         CH.sub.2 CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9                                                87.5˜89                          203     COCH.sub.3                                                                            "         n-C.sub.8 H.sub.17                                                                         132˜134                          204     "       "         CH.sub.2 CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9                                                73˜76                            205     Cl      "                                                                                        ##STR123##  188˜190                          206     "       F         n-C.sub.5 H.sub.11                                                                         188˜191                          207     "       CH.sub.2 Cl                                                                             n-C.sub.7 H.sub.15                                                                         143˜145                          208     CH.sub.3                                                                              H         CH.sub.2 CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9                                                .sub.n D.sup.20 1.5611                 209     Cl      "                                                                                        ##STR124##  157˜160                          210     "       "                                                                                        ##STR125##  122˜126                          211     H       CN        n-C.sub.8 H.sub.17                                                                         111˜112                          212     "       "                                                                                        ##STR126##  105˜107                          213     F       H         "            94˜99                            214     OCH.sub.3                                                                             "                                                                                        ##STR127##  173˜175                          215     "       "                                                                                        ##STR128##  191.5˜194                        216     "       "                                                                                        ##STR129##  195˜198                          __________________________________________________________________________

Of these compounds, preferred are compounds of the general formula (I)wherein X stands for a hydrogen atom, a chlorine atom, a fluorine atom,a C₁₋₄ -alkyl group, a C₁₋₃ -alkoxy group, an ethynyl group, an acetylgroup or a cyano group; Y stands for a hydrogen atom, a chlorine atom, afluorine atom, a C₁₋₃ -alkyl group, a C₁₋₃ -alkoxy group, a C₂₋₃-alkynyl group or a cyano group; and R stands for a C₁₋₉ -alkyl group, atrimethylsilylpropyl group, a phenyl group which may be substituted withone or two chlorine or fluorine atoms or C₁₋₄ -alkyl groups or a benzylgroup substituted with one or two chlorine or fluorine atoms or one ortwo C₁₋₄ -alkyl groups.

More preferred are compounds of the general formula (I) wherein X standsfor a hydrogen atom, a chlorine or fluorine atom, a methyl group, amethoxy group, an ethynyl group, a cyano group or an acetyl group; Ystands for a hydrogen atom, a chlorine or fluorine atom, an ethynylgroup, a propynyl group or a cyano group; and R stands for a C₄₋₉ -alkylgroup, a trimethylsilylpropyl group, a phenyl group which may besubstituted with a chlorine or fluorine atom or a methyl group or abenzyl group substituted with one or two chlorine or fluorine atoms orone or two methyl groups.

One group of most preferred compounds are compounds of the generalformula (I) wherein X stands for a hydrogen atom, a chlorine or fluorineatom or a methyl group; Y stands for a hydrogen atom, an ethynyl groupor a propynyl group; and R stands for a C₄₋₈ -alkyl group or amethylbenzyl group.

Another group of most preferred compounds are compounds of the generalformula (I) wherein X stands for a chlorine or fluorine atom, a methylgroup, an ethynyl group or a cyano group; Y stands for a hydrogen atomor a chlorine or fluorine atom; and R stands for a C₄₋₈ -alkyl.

Still another group of most preferred compounds are compounds of thegeneral formula (I), wherein X stands for a chlorine or fluorine atom, amethoxy group or an acetyl group; Y stands for a hydrogen atom; and Rstands for a C₄₋₈ -alkyl group a benzyl group substituted with one ortwo chlorine or fluorine atoms or one or two methyl groups.

Still another group of most preferred compounds are compounds of thegeneral formula (I), wherein X stands for a hydrogen atom or a chlorineor fluorine atom; Y stands for a cyano group, an ethynyl group or apropynyl group; and R stands for a C₄₋₉ -alkyl group.

Still another group of most preferred compounds are compounds of thegeneral formula (I), wherein X stands for a hydrogen atom, a chlorineatom, a fluorine atom, a methyl group or a methoxy group; Y stands for ahydrogen atom; and R stands for a benzyl group substituted with one ortwo chlorine or fluorine atoms or one or two methyl groups.

Still another group of most preferred compounds are compounds of thegeneral formula (I), wherein X stands for a chlorine atom; Y stands fora hydrogen atom or a chlorine or fluorine atom; and R stands for a C₄₋₉-alkyl group.

Still another group of most preferred compounds are compounds of thegeneral formula (I), wherein X stands for a chlorine atom; Y stands fora hydrogen atom; and R stands for a C₅₋₆ -alkyl group.

The most preferred compounds are:

6-Chloro-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

2-Hexanesulfonyl-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

7-Ethynyl-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

6-Chloro-7-fluoro-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

7-Ethynyl-6-chloro-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

6-Methoxy-2-octanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

6-Cyano-2-heptanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

6-Acetyl-2-heptanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

6-Chloro-7-fluoro-2-pentanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

The compounds of the present invention can be prepared by oxidizing acompound represented by the general formula (II) ##STR130## wherein X, Yand R are as defined with respect to the general formula (I).

The oxidation of the compounds of the general formula (II) can beperformed by any method employed for oxidation of organic sulfidecompounds.

Examples of the employable oxidizing agents are hydrogen peroxide,organic peracids such as m-chloroperbenzoic acid, "OXONE" (trade name, areagent containing potassium hydrogen peroxosulfate marketed by Du PontCompany), etc.

In addition to the oxidation reagent, an acid catalyst such as aceticacid, a metallic catalyst such as sodium tungstate, for instance, can beused in order to promote the oxidation reaction.

Examples of the solvents used for the oxidation reaction are water;halogenated hydrocarbon such as dichloromethane, chloroform, carbontetrachloride, chlorobenzene, etc.; fatty acids such as acetic acid,propionic acid, etc.; ketones such as acetone, methylethyl ketone, etc.;amides such as dimethylformamide, dimethylacetamide, etc.; alcohols suchas methyl alcohol, ethyl alcohol, etc.; hydrocarbons such as hexane,petroleum ether, benzene, etc.

Oxidation is carried out in a temperature range of -20° C. to theboiling temperature of the used solvent. The amount of the usedoxidizing agent is usually twice the molar quantity of the used compoundof the general formula (II) or more, but there is no strict limitationtherefor.

The compounds of the general formula (II) are novel substances and canbe prepared from a compound of the general formula (III): ##STR131##wherein R is as defined above, by the four methods described belowdepending upon the kind of substituents.

The compound of the general formula (III) can be prepared by a generallyemployed method for preparing known 1,3,4-thiadiazoles in accordancewith the following reaction scheme: ##STR132## wherein R is as definedabove and U¹ stands for a halogen atom, a benzenesulfonyloxy group, asubstituted benzenesulfonyloxy group; and U² stands for a halogen atom.

The four methods for preparing compounds of the general formula (II) areas follows.

Process A

Compounds of the general formula (II) wherein R is as defined above, Xis a hydrogen atom, a halogen atom or an alkyl group (designated as X¹);and Y is an alkyl group or a haloalkyl group (designated as Y¹) can beprepared by reacting a compound of general formula (III) with a β-ketoester derivative of the general formula (IV): ##STR133## wherein R is asdefined above, X¹ and Y¹ are as defined above under Process A, and R¹stands for an alkyl group.

The reaction is carried out in a high-boiling solvent, or in thepresence of a condensation reagent such as polyphosphoric acid, borontrifluoride etherate, sulfuric acid, etc. in the presence or absence ofa relatively high boiling solvent such as xylene.

Compounds of the general formula (IV) are known or otherwise can beprepared by a conventional process. Some of them are commerciallyavailable.

Of the compounds of the general formula (V), compounds, of which X¹ is ahalogen atom, can be prepared by halogenating a corresponding compoundof which X¹ is a hydrogen atom. As halogenating agents, chlorine,bromine, sulfuryl chloride, iodine monochloride, etc. can be used, forinstance. If desired, a metal halide such as zinc chloride, ferrichalide, etc. and pyridine, etc. can be used as a catalyst. Also,pyridine, zinc chloride, etc. can be used as a hydrogen halide remover.

A halogen atom as a substituent X¹ in the general formula (V),preferably an iodine, can be converted to a cyano group. As a preferredcyanizing agent, sodium cyanide and cuprous cyanide are simultaneouslyused in the presence of dimethylformamide solvent.

Process B

Compounds of the general formula (II), wherein X is a hydrogen atom, ahalogen atom, a linear or branched alkyl group, a phenyl group, analkoxy group, a phenoxy group or a trifluoroalkoxy group (designated asX²); and Y is a hydrogen atom, can be prepared by reacting a compound ofthe general formula (III) with a β-formyl ester derivative or a2-propenoate ester derivative (VI): ##STR134## wherein R is as definedabove, X² is as defined above under Process B, R² stands for an alkylgroup, and R³ stands for a hydroxy group or an alkoxy group. Thereaction can be carried out in the same manner as in the above-describedProcess A.

Compounds of the general formula (VII) wherein X² is a halogen atom canbe prepared by halogenating a compound of the general formula (VII)wherein X² is a hydrogen atom. Further, the halogen atom, preferably aniodine atom as a substituent X² can be converted to a cyano group or analkynyl group by a conventional method. The halogenation and thecyanization can be effected as described above with respect to ProcessA.

Compounds of the general formula (VII) wherein X² is an alkynyl groupcan be prepared by reacting a compound of the general formula (VII)wherein X² is a halogen atom, preferably, an iodine atom, with an alkynecompound such as an alkylacetylene, ethynyltrimethylsilane, etc. in thepresence of a catalyst such as bis(triphenylphosphine)palladium (II)chloride, cuprous iodide, etc. and a dehydrochlorinating reagent such astriethylamine. If necessary, the protecting group such as trimethylsilylwhich is bonded to the alkynyl group is removed with a base such aspotassium carbonate, tetralkylammonium fluoride, etc.

Compounds of the general formula (VI) are known or can be easilyprepared by any conventional method. Some of them are commerciallyavailable.

Process C

Compounds of the general formula (II), wherein R is as defined above, Xis a hydrogen atom or an alkyl group (designated as X⁴), Y is a halogenatom (designated as Y²) or an alkynyl group or a cyano group (designatedas Y³) can be prepared by the following steps: ##STR135## wherein R isas defined above, X⁴, Y² and Y³ are as defined above under Process C,and R⁴ stands for a phenyl group or a substituted phenyl group.

The reaction of a compound of the general formula (III) and a compoundof the general formula (VIII) is carried out in a relativelyhigh-boiling solvent in accordance with the procedure described inPharmacie 33, H 11˜13 (1978). A compound of the general formula (IX) canbe converted to the corresponding compound of the general formula (X).If desired, the compound of the general formula (X) is subjected tohalogen exchange. The halogen atom, preferably an iodine atom, can beconverted to an alkynyl or a cyano group.

Examples of the usable halogenating agents are phosphorus oxychloride,phosphorus pentachloride, etc. If desired, a solvent such as toluene, ahydrogen halide remover such as N,N-dimethylaniline, etc. can be used.Halogen exchange can be performed using sodium iodide, hydroiodic acid,potassium fluoride, etc.

Compounds of the general formula (XI) wherein Y³ is an alkynyl group ora cyano group can be prepared by converting the halogen atom Y²,preferably an iodine atom, of a compound of the general formula (X) toan alkynyl group or a cyano group in accordance with the alkynylationprocedure described in Process B or the cyanization procedure describedin Process A.

The hydrogen atom as a substituent X⁴ of a compound of the generalformula (IX), (X) or (XI) can be replaced with a halogen atom.##STR136## wherein R is as defined above, X⁵ stands for a halogen atomand Y⁴ stands for a hydroxy group, a halogen atom, an alkynyl group orcyano group. A halogen atom as the substituent X⁵, preferably an iodineatom, can be converted to a cyano group.

The halogenation or cyanization can be performed by the same procedureas the halogenation or cyanization of the 6-position described inProcess A. A compound of the general formula (XIII) wherein Y⁴ is ahydroxy group can be halogenated by the same procedure as thehalogenation of the 7-position of a compound of the general formula(IX).

Compounds of the general formula (IX) wherein X⁴ is a hydrogen atom, canbe nitrated, and thereafter the hydroxy group at the 7-position can beconverted to a halogen atom, and further the halogen atom can beconverted to an alkoxy group or an alkylamino group. ##STR137## whereinR is as defined above. Y^(2b) stands for a halogen atom, Y⁵ stands foran alkoxy group or an alkylamino group.

Compounds of the general formula (XIV) can be prepared by treating acompound of the formula (IXb) with fuming nitric acid, in the presenceof a solvent such as acetic acid if desired Compounds of the formula(XV) can be prepared in the same manner as the preparation of compoundsof the formula (X). Compounds of the formula (XVI) can be prepared byreacting a compound of the formula (XV) with an alcohol or an alkylaminein the presence of a catalyst such as pyridine, and a solvent ifdesired.

Compounds of formula (VIII) are known or can be prepared by anyconventional method.

Process D

Compounds of the formula (II) wherein X is an acetyl group can beprepared by the following process: ##STR138## wherein R is as definedabove with respect to the general formula (I), R⁵ and R⁶ stand for analkyl group.

That is, a compound of the general formula (III) and adialkylformamidodialkylacetal of the formula (XVII) are reacted to forma compound of the general formula (XVIII), and the latter is reactedwith diketene to form a compound of the general formula (XIX).

The compounds of the present invention can be used as anagricultural-horticultural fungicide per se. However, they are usuallyprepared into a preparation in the form of dust, emulsifiableconcentrate, granule or pellet by adding a carrier, surfactant,dispersant, or adjuvant by a conventional method.

Preferred carriers include solid carriers such as talc, bentonite, clay,kaolin, diatomaceous earth, white carbon, virmiculite, slaked lime,siliceous sand, ammonium sulfate, urea, etc. and liquid carriers such asisopropyl alcohol, xylene, cyclohexanone, etc.

Examples of the employable surfactants and dispersants are alcoholsulfate salts, alkylsulfonic acid salts, lignosulfonic acid salts,polyoxyethyleneglycol ether, polyoxyethylene alkylaryl ether,polyoxyethylene sorbitan monoalkylate, etc. As adjuvants, carboxymethylcellulose, polyethylene glycol, gum arabic, etc. for instance can beused. The preparations are diluted to a suitable concentration andsprayed. Or otherwise, they are directly applied.

The concentration of the active ingredient can be varied as occasiondemands. However, generally 0.5˜20% by weight is suitable in dust orgranular preparations and 5˜80% by weight is suitable in emulsion orwater-dispersible preparations.

The application amount of the agricultural-horticultural fungicide ofthe present invention is varied depending upon species of the usedcompound, kind of disease, condition and degree of affection,environmental conditions, type of the used preparation, etc. In the caseof dust or granular preparations, which are applied as they are, theconcentration of the active ingredient may well be selected in the rangeof 10˜500 g per 10 ares. In the case of an emulsion or a water-dispersedpreparation, which is used in the form of liquid, the concentration isselected in the range of 10˜2000 ppm.

The compounds of the present invention exhibit a remarkable effect forAlternaria sooty spot of Chinese mustard (Brassica rapa var. pervidis)caused by Alternaria brassicicola, Alternaria leaf spot of apple, blackspot disease of pear, cucumber gray mold, cucumber downy mildew, riceblast, late bright of tomato and potato, gray mold of egg plant andgrape, etc., as well as disease injury disseminated through soil orseeds. The effect is exhibited both preventive and curative, and isdurable. Further, the compounds of the present invention are highlynon-toxic to homoiothermic animals and aquatic animals.

SPECIFIC DESCRIPTION OF THE INVENTION

Now the invention will be described specifically with respect topreparation of the compounds and formulation ofagricultural-horticultural fungicidal compositions by way of workingexamples. In these examples percentages referred to are all by weight.

PREPARATION EXAMPLE 1 Synthesis of2-(4-chlorobenzylsulfonyl)-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 2)

In 500 ml of chloroform, 16.4 g of2-(4-chlorobenzylthio)-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneand 26.2 g of m-chloroperbenzoic acid were dissolved and the mixture wasstirred for 10 hours at -10°˜5° C. An aqueous solution of sodiumhydrogen carbonate was added to the mixture to quench the reaction.Chloroform was added for extraction, the organic layer was washed withwater and dried over anhydrous sodium sulfate. The solvent was distilledoff, the residue was purified by column chromatography on a silica gelwith an ethyl acetate:toluene (1:9) mixture as an eluant. The solventwas distilled off and 9.5 g of2-(4-chlorobenzylsulfonyl)-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained m.p. 192°˜194° C., yield 53%.

PREPARATION EXAMPLE 2 Synthesis of2-benzenesulfonyl-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 40)

In 165 ml of methanol, 4.1 g of2-phenylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. A dispersion of 40.3 g of OXONE® suspended in 165 ml of waterwas added to the methanol solution, and the resulting mixture was warmedto 60° C. and stirred for 2 hours. After cooling, chloroform was addedfor extraction, the organic layer was washed with a sodium thiosulfateaqueous solution, a sodium hydrogen carbonate aqueous solution and waterrespectively. After the organic layer was dried over anhydrous sodiumsulfate, the solvent was distilled off. The residue was recrystallizedfrom a toluene/ethanol (1:1) mixture and thus 1.2 g of2-benzenesulfonyl-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained m.p. 198°˜200° C. Yield 26%.

PREPARATION EXAMPLE 3 Synthesis of7-fluoro-2-heptanesulfonyl-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 33)

In 270 ml of methanol, 4.7 g of7-fluoro-2-heptylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas dissolved. A dispersion of 77.8 g of OXONE® in 270 ml of water wasadded to the methanol solution. The residue obtained by the sameprocedure as in Example 2 was purified by column chromatography on asilica gel column with an ethylacetate/n-hexane (2:3) mixture as aneluent. The solvent was distilled off and the residue was recrystallizedfrom ethanol, and thus 2.7 g of7-fluoro-2-heptanesulfonyl-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 143°˜146° C. Yield 57%.

PREPARATION EXAMPLE 4 Synthesis of2-(4-chlorobenzylthio)-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 35 ml of water and 70 ml of ethanol, 12.8 g of2-amino-5-mercapto-1,3,4-thiadiazol and 43 g of sodium hydroxide wereadded. To this mixture, 14.8 g of 4-chlorobenzyl chloride was added andthe mixture was stirred at room temperature for 1 hour. Water was addedand the reaction mixture was filtered The residue was washed with waterand an ethanol/n-hexane (1:1) mixture, and was dried under reducedpressure, and thus 23.1 g of2-amino-5-(4-chlorobenzylthio)-1,3,4-thiadiazole was obtained. m.p.162°˜164° C. Yield 93%.

Twenty point two (20.2) g of the thus obtained2-amino-5-(4-chlorobenzylthio)-1,3,4-thiadiazole and 12.2 g of ethylacetoacetate were mixed with 24 g of polyphosphoric acid and the mixturewas stirred at 130°˜150° C. for 45 minutes. After cooling, water wasadded to the mixture, the mixture was extracted with chloroform, and theorganic layer was washed with a sodium hydrogen carbonate aqueoussolution and water respectively. The organic layer was dried overanhydrous sodium sulfate, and the solvent was distilled off. The residuewas recrystallized from ethanol and thus 21.3 g of2-(4-chlorobenzylthio)-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained m.p. 138.5°˜139.5° C. Yield 84%.

PREPARATION EXAMPLE 5 Synthesis of2-phenylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In a mixture of 20 ml of water and 30 ml of ethanol, 7.3 g of thiophenoland 4.5 g of potassium hydroxide were added. To this solution, 11.7 g of2-amino-5-bromo-1,3,4-thiadiazole was added, and the mixture was heatedto 82° C. and stirred for 2 hours. After cooling, water was added andthe mixture was filtered. The residue was washed with water and n-hexanerespectively, dried under reduced pressure, and thus 10.8 g of2-amino-5-phenylthio-1,3,4-thiadiazole was obtained. m.p. 202°˜203° C.Yield 77%.

Seven point two (7.2) g of the thus obtained2-amino-5-phenylthio-1,3,4-thiadiazole and 4.9 g of ethyl3-hydroxy-2-methyl-2-propenoate were mixed with 13 g of polyphosphoricacid. By the same procedure as in Preparation Example 2, 5.9 g of2-phenylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained m.p. 141°˜143° C. Yield 58%.

PREPARATION EXAMPLE 6 Synthesis of7-fluoro-2-heptylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 32 ml of water and 32 ml of ethanol, 27.2 g of2-amino-5-mercapto-1,3,4-thiadiazole and 9.0 g of sodium hydroxide wereadded. To this solution, 45.2 g of 1-iodoheptane was added, and themixture was stirred at 60° C. for 2 hours. After cooling, water wasadded to the mixture and the mixture was filtered. The residue waswashed with water, dried under reduced pressure, and recrystallized froman ethanol/n-hexane (1:1) mixture. Thus 36.1 g of2-amino-5-heptylthio-1,3,4-thiadiazole was obtained. m.p. 112°˜113° C.Yield 78%.

A mixture of 19.7 g of the thus obtained2-amino-5-heptylthio-1,3,4-thiadiazole, 40.9 g ofbis(2,4,6-trichlorophenyl)-2-methyl-malonate and 55 ml of chlorobenzenewas stirred at 140°˜144° C. for 45 minutes. After cooling, n-hexane wasadded thereto, the precipitate was collected by filtration. Furthern-hexane was added to the filtrate, and the precipitate was collectedThe collected precipitates were combined. The combined precipitate waswashed with n-hexane and thus 21.2 g of2-heptylthio-7-hydroxy-6-methyl-5H-1,3,4-thiadiazolo-[3,2-a]pyrimidin-5-one was obtained. m.p. 141°˜143° C. Yield 78%.

A mixture of 19.5 g of the thus obtained2-heptylthio-7-hydroxy-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one,38 g of phosphorus oxychloride and 13.6 g of phosphorus pentachloridewas warmed to 77°˜88° C. and was stirred for 2 hours. The reactionsolution was concentrated under reduced pressure, thereafter the residuewas dissolved in toluene, and the solution was washed with a potassiumcarbonate aqueous solution and water respectively. After the solutionwas dried over anhydrous sodium sulfate, the solvent was distilled offand the residue was purified by column chromatography on a silica gelcolumn with an ethyl acetate/n-hexane (2:3) mixture as an eluent. Afterthe solvent was distilled off, 19.0 g of7-chloro-2-heptylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 79°˜81° C. Yield 92%.

A solution of 8.6 g of the thus obtained7-chloro-2-heptylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one,3.0 g of spray dry potassium fluoride and 32 ml of sulfolane was heatedat 205°˜225° C. in a stream of nitrogen for 1 and half hours. Aftercooling, water was added to the mixture, and the mixture was extractedwith toluene. The toluene layer was collected and washed with water. Thetoluene phase was dried over anhydrous sodium sulfate, the solvent wasdistilled off. The residue was purified by column chromatography on asilica gel column with an ethyl acetate/n-hexane (1:3) mixture as aneluent. After the solvent was distilled off, 5.2 g of7-fluoro-2-heptylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 78°˜91° C. Yield 63%.

PREPARATION EXAMPLE 7 Synthesis of2-hexanesulfonyl-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 115)

In 225 ml of methanol, 6.6 g of2-hexylthio-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas dissolved. A dispersion of 51.2 g of OXONE® suspended in 180 ml ofwater was added to the methanol solution, and the resulting mixture waswarmed to 60°˜65° C. and stirred for 50 minutes. After cooling, themixture was extracted with chloroform, and the organic layer was washedwith a sodium thiosulfate aqueous solution and water respectively, anddried over anhydrous sodium sulfate. The solvent was distilled off andthe residue was purified by silica gel column chromatography using anethyl acetate/toluene mixture as an eluent, and was recrystallized fromethanol. Thus 2.6 g of2-hexanesulfonyl-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 122°˜125° C. Yield 41%.

PREPARATION EXAMPLE 8 Synthesis of6-chloro-7-fluoro-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 121)

In 20 ml of acetic acid, 2.8 g of6-chloro-7-fluoro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneand 0.14 g of sodium tungstate dihydrate were dissolved. To this aceticacid solution, 8.9 g of a 20% hydrogen peroxide solution was addeddropwise over a 20 minute period. The solution was warmed to 60°˜65° C.and stirred for 45 minutes. After cooling, the solution was diluted withwater and extracted with chloroform. The organic layer was washed withwater once, and was treated in the same manner as in Preparation Example7. The thus obtained residue was recrystallized from ethanol and 2.0 gof6-chloro-7-fluoro-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 185°˜188° C. Yield 65%.

PREPARATION EXAMPLE 9 Synthesis of2-heptanesulfonyl-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 94)

In 55 ml of methanol, 3.3 g of2-heptylthio-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. A dispersion of 19.4 g of OXONE® suspended in 0 ml of waterwas added to the methanol solution, and the resulting mixture was warmedto 65° C. and stirred for 1 hour. The residue obtained by the sameprocedure as in Preparation Example 7 was recrystallized from ethanoland thus 2.7 g of2-heptanesulfonyl-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 106°˜109° C. Yield 51%.

PREPARATION EXAMPLE 10 Synthesis of6-ethynyl-2-heptanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(Compound 87)

In 180 ml of methanol, 2.8 g of6-ethynyl-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. A dispersion of 20 g of OXONE® in 66 ml of water was added tothe methanol solution and the resulting mixture was stirred for 24 hoursat room temperature. The residue obtained by the same procedure as inPreparation Example 7 was separated by silica gel column chromatographyusing an ethyl acetate/toluene mixture as an eluent and wasrecrystallized from an ethanol/chloroform mixture, and thus 1.3 g of6-ethynyl-2-heptanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 180°˜182° C. Yield 39%.

PREPARATION EXAMPLE 11 Synthesis of2-hexylthio-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 190 ml of ethanol and 240 ml of water, 81.5 g of2-amino-5-mercapto-1,3,4-thiadiazole and 26.9 g of sodium hydroxide wereadded. To this solution, 99 g of 1-bromohexane was added and theresulting mixture was warmed to 60°˜70° C. and stirred for 2 hours.After cooling, water was added to the reaction mixture, and theresulting solution was filtered. The residue was washed with water anddried under reduced pressure. The dried residue was recrystallized froman ethanol/hexane mixture, and thus 100.5 g of2-amino-5-hexylthio-1,3,4-thiadiazole was obtained. m.p. 113°˜115° C.Yield 77%.

A mixture of 65.2 g of the thus obtained2-amino-5-hexylthio-1,3,4-thiadiazole, 141.7 g ofbis(2,4,6-trichlorophenyl) malonate and 240 ml of chlorobenzene washeated to 137°˜140° C. and stirred for 1 hour. After cooling, hexane wasadded to the mixture, and the formed precipitate was separated byfiltration, the residue was washed with hexane, and thus 74.7 g of2-hexylthio-7-hydroxy-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one wasobtained. m.p. 187°˜192° C. Yield 87%.

A mixture of 23.5 g of the thus obtained2-hexylthio-7-hydroxy-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one, 17.8g of phosphorus pentachloride and 50.4 g of phosphorus oxychloride washeated to 65°˜90° C. and was stirred for 2 hours. The reaction mixturewas concentrated under reduced pressure. The residue was dissolved intoluene. The solution was washed with a potassium carbonate aqueoussolution and water respectively, and dried over anhydrous sodiumsulfate. The solvent was distilled off, and the residue was separated bysilica gel column chromatography using an ethyl acetate/toluene mixtureas an eluent, and 10.2 g of7-chloro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 95°˜96° C. Yield 41%.

A solution of 8.4 g of the thus obtained7-chloro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one and88.2 g of a 57% hydroiodic acid aqueous solution was heated to 95°˜110°C. and stirred for 2 hours. After cooling, the solution was filtered.The residue was washed with water and dissolved in toluene. The toluenesolution was washed with a sodium hydrogen carbonate aqueous solution, asodium thiosulfate aqueous solution and water respectively and driedover anhydrous sodium sulfate. The solvent was distilled off and thus9.8 g of 80% pure7-iodo-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. Yield 72%.

Into a solution of 8.6 g of the thus obtained7-iodo-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one, 11 g oftriethylamine, 0.15 g of bis(triphenylphosphine)palladium(II) chloride,0.04 g of cuprous iodide and 33 ml of tetrahydrofurane, 2.6 g of1-propyne was introduced through a bubbling glass tube underice-cold-water chilling and constant stirring over a 1 hour period.Thereafter, the solution was further stirred at room temperature for 30minutes, and 0.23 g of bis(triphenylphosphine)palladium(II) chloride and0.06 g of cuprous iodide were added. The solution was stirred furtherfor 4 hours. Then toluene was added, and the solution was filtered, andthe filtrate was concentrated under reduced pressure. The residue wasdissolved in toluene, the solution was washed with water and dried overanhydrous sodium sulfate. The solvent was distilled off and the residuewas recrystallized from an ethanol/hexane mixture and thus 3.9 g of7-(1-propynyl)-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 94°˜97° C. Yield 72%.

PREPARATION EXAMPLE 12 Synthesis of6-chloro-7-fluoro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

A solution of 30 g of2-hexylthio-7-hydroxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one, 21.3 gof sulfuryl chloride, 0.85 g of ferric chloride and 113 g of phosphorusoxychloride was heated to 110° C. and stirred for 1.5 hours. Aftercooling, the reaction solution was concentrated under reduced pressure.To the residue, toluene and water were added, and extraction was carriedout. The organic layer was washed with water, a sodium hydrogencarbonate aqueous solution and water respectively, and dried overanhydrous sodium sulfate. The solvent was distilled off and the residuewas purified by silica gel column chromatography using an ethylacetate/toluene mixture as an eluent. Thus 18.8 g of6,7-dichloro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. Yield 75%.

A solution of 4.4 g of the thus obtained6,7-dichloro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one,2.2 g of potassium fluoride and 20 ml of sulfolane was heated to185°˜200° C. and stirred for 45 minutes. After cooling, toluene andwater were added to the reaction solution and extraction was carriedout. The organic layer was washed with water and dried over anhydroussodium sulfate. The solvent was distilled off and the residue wasseparated by silica gel column chromatography using an ethylacetate/toluene mixture as an eluent. Thus 3.0 g of6-chloro-7-fluoro-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. m.p. 105°˜111° C. Yield 71%.

PREPARATION EXAMPLE 13 Synthesis of2-heptylthio-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 185 ml of ethanol and 185 ml of water, 68.0 g of2-amino-5-mercapto-1,3,4-thiadiazole and 22.4 g of sodium hydroxide wereadded. To this mixture, 84.6 g of 1-bromoheptane was added, and theresulting mixture was warmed to 60° C. and stirred for 2 hours. Aftercooling, water was added and the mixture was filtered. The residue waswashed with water, dried under reduced pressure, and recrystallized froman ethanol/hexane mixture. Thus 90.2 g of2-amino-5-heptylthio-1,3,4-thiadiazole was obtained. m.p. 112°˜113° C.Yield 78%.

A mixture of 4.7 g of 2-amino-5-heptylthio-1,3,4-thiadiazole, 3.3 g ofpropyl 3-hydroxy-2-methoxy-2-propenoate and 12 g of polyphosphoric acidwas heated to 130°˜135° C. and stirred for 30 minutes. After cooling,water and chloroform were added to the mixture and extraction wascarried out. The organic layer was washed with a sodium hydrogencarbonate aqueous solution and water respectively, and dried overanhydrous sodium sulfate. The solvent was distilled off, and the residuewas separated by silica gel column chromatography using an ethylacetate/toluene mixture as an eluent. Thus 4.0 g of2-heptylthio-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 68°˜71° C. Yield 64%.

PREPARATION EXAMPLE 14 Synthesis of6-ethynyl-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

A mixture of 20.1 g of 2-amino-5-heptylthio-1,3,4-thiadiazole, 20.0 g ofethyl 3-ethoxypropenoate and 23 g of polyphosphoric acid was heated to130°˜140° C. and stirred for 30 minutes. The residue obtained by thesame procedure as in Preparation Example 13 was purified by silica gelcolumn chromatography using an ethyl acetate/toluene mixture as aneluent. Thus 12.6 g of2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was obtained.Yield 51%.

In 65 ml of acetic acid, 12.5 g of the thus obtained2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]-pyrimidin-5-one was dissolved.To this solution, 10.5 g of zinc chloride was added, and a solution of10.5 g of iodine monochloride in 20 ml of acetic acid was added dropwiseto the solution. Thereafter, the solution was warmed to 70°˜80° C. andstirred for 1.5 hours. After cooling, chloroform and water were addedand extraction was carried out. The organic layer was washed with asodium hydrogen carbonate aqueous solution, a sodium thiosulfate aqueoussolution and water respectively, and dried over anhydrous sodiumsulfate. The solvent was distilled off and the residue was purified bysilica gel column chromatography using an ethyl acetate/toluene mixtureas an eluent. Thus 9.4 g of2-heptylthio-6-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one. Yield52%.

In a mixture of 50 ml of triethylamine and 100 ml of tetrahydrofurane,8.0 g of the thus obtained2-heptylthio-6-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. To this solution, 0.68 g ofbis(triphenylphosphine)palladium(II) chloride and 0.2 g of cuprousiodide were added as catalysts. To this mixture, a solution of 3.9 g ofethynyltrimethylsilane in 20 ml of triethylamine was added dropwise. Themixture was warmed to 60°˜70° C. and stirred for 1 hour. Thereafter,further the same amounts as above of the catalysts andethynyltrimethylsilane were added, and the mixture was stirred at60°˜70° C. for 3 hours. After cooling, the reaction mixture wasfiltered, and the filtrate was concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography using an ethylacetate/toluene mixture as an eluent, and 5.9 g of2-heptylthio-6-trimethylsilylethynyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. Yield 80%.

In 100 ml of tetrahydrofurane, 5.4 g of the thus obtained2-heptylthio-6-trimethylsilylethynyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one,and the solution was cooled to -65° C. in an acetone-dry ice bath. Tothe cooled solution, a solution of 0.93 g of tetrabutylammonium fluoridein 200 ml of tetrahydrofurane was added dropwise. The solution wasstirred at -70°˜-65° C. for 1 hour. After the solution was brought toroom temperature, the solution was filtered, and the filtrate wasconcentrated under reduced pressure. The residue was purified by silicagel column chromatography using an ethyl acetate/toluene mixture as aneluent and thus 3.0 g of6-ethynyl-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 140°˜142° C. Yield 70%.

PREPARATION EXAMPLE 15

Synthesis of2-hexanesulfonyl-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

In 50 ml of acetic acid, 1.9 g of2-hexylthio-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneand 0.1 g of sodium tungstate dihydrate were dissolved. The solution waswarmed to 50° C., and 3.1 g of a 30% hydrogen peroxide solution wasadded dropwise, and thereafter the solution was stirred at 52° C. for 1hour. The reaction mixture was poured into 500 ml of water, and theformed precipitate was collected by filtration. The precipitate waswashed with a sodium hydrogen sulfite aqueous solution and water, andrecrystallized from ethanol. Thus 1.5 g of2-hexanesulfonyl-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneas colorless prismatic crystals was obtained. m.p. 150°˜152° C. Yield71%.

PREPARATION EXAMPLE 16

Synthesis of6-acetyl-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

In 30 ml of acetic acid, 1.8 g of6-acetyl-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. To this solution, 2.0 g of a 30% hydrogen peroxide solutionand 0.1 g of sodium tungstate dihydrate were added, and the solution wasstirred at 55°˜60° C. for 2 hours. The reaction mixture was extractedwith chloroform, and the organic layer was washed with water, a sodiumthiosulfate aqueous solution and water in this order, and dried overanhydrous sodium sulfate. The solvent was distilled off and the residuewas recrystallized from an ethanol/benzene mixture. Thus 1.0 g of6-acetyl-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 124°˜125° C. Yield 50%.

PREPARATION EXAMPLE 17 Synthesis of6-cyano-2-heptanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

In 50 ml of acetic acid, 2.1 g of6-cyano-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one and 0.1g of sodium tungstate dihydrate were dissolved. To this solution, 2.3 gof a 30% hydrogen peroxide solution was added dropwise so that thetemperature of the solution did not exceed 50° C. Thereafter, thesolution was stirred at 50° C. for 3 hours.

After the reaction was finished, water was added to the reactionmixture, and the deposited crystals were collected by filtration. Thiscrude crystals were recrystallized from ethanol and 2 g of6-cyano-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one. m.p.130°˜132° C. Yield 85%.

PREPARATION EXAMPLE 18 Synthesis of7-cyano-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

In 40 ml of acetic acid, 2.2 g of7-cyano-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved, 0.12 g of sodium tungstate dihydrate was added to thesolution, and the solution was warmed to 45° C. and stirred. To thissolution, 4.3 g of a 30% hydrogen peroxide mixed with 20 ml of aceticacid was added dropwise. Thereafter, the solution was stirred at 45°˜50°C. for 2 hours. After cooled to room temperature, the solution wasextracted with chloroform and water. The organic layer was washed with asodium thiosulfate aqueous solution and water respectively. After driedover anhydrous sodium sulfate, the solvent was distilled off. Theresidue was recrystallized from ethanol, and thus 1.6 g of7-cyano-2-hexanesulfonyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 144°˜146° C. Yield 65%.

PREPARATION EXAMPLE 19 Synthesis of2-hexylthio-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

Seventy-six (76) grams of 2-amino-5-hexylthio-1,3,4-thiadiazole and 170g of bis(2,4,6-trichlorophenyl) malonate ester were mixed with 200 ml ofchlorobenzene, the mixture was stirred under refluxing for 1 hour. Afterthe reaction was finished, the reaction mixture was cooled, and theformed precipitate was collected by filtration and washed with ether.Thus 82 g of white powder of2-hexylthio-7-hydroxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. m.p. 193°˜197° C. Yield 82%.

In 800 ml of acetic acid, 78 g of2-hexylthio-7-hydroxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wassuspended. To this suspension, 120 ml of fuming nitric acid was addeddropwise at room temperature. After stirred for 3 hours, the reactionmixture was cooled, and the formed precipitate was collected byfiltration and washed with ether. Thus 84.5 g of colorless filament-likecrystals of2-hexylthio-7-hydroxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.m.p. 139°˜141° C. Yield 94%.

In 240 ml of phosphorus oxychloride, 66 g of2-hexylthio-7-hydroxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas suspended, and 24 g of N,N-dimethylaniline was added dropwise to thesuspension at room temperature. The mixture was stirred for 2 hoursunder refluxing. The phosphorus oxychloride in the reaction mixture wasdistilled off under reduced pressure at 50° C. The residue was pouredinto 1 of ice water, and deposited crystals were collected byfiltration. The crystals were recrystallized from ethanol, and thus 58.4g of pale yellow scaly crystals of7-chloro-2-hexylthio-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-Onewas obtained. m.p. 84.5°˜86° C. Yield 83%.

To 50 ml of methanol, 3.0 g of7-chloro-2-hexylthio-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneand 1.0 g of pyridine were added, and the mixture was stirred underrefluxing for 30 minutes. Water was added to the reaction mixture andthe organic layer was extracted with ethyl acetate The ethyl acetatesolution was dried over anhydrous magnesium sulfate, and the solvent wasdistilled off. The residue was purified by silica gel columnchromatography using an ethyl acetate/hexane mixture as an eluent. Thus1.9 g of brown transparent viscous liquid of2-hexylthio-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. Yield 63%.

PREPARATION EXAMPLE 20 Synthesis of6-acetyl-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 60 ml of ethanol, 4.4 g of 2-amino-5-hexylthio-1,3,4-thiadiazole, and2.4 g of N,N-dimethylformamidodimethylacetal were dissolved, and thesolution was refluxed for 2 hours. After the reaction mixture was cooledto room temperature, the formed crystals were collected by filtration,washed with ethanol and dried. Thus 4.4 g ofN'-2-(5-hexylthio-1,3,4-thiadiazolyl)-N,N-dimethylformamidin wasobtained. m.p. 89°˜91° C. Yield 81%.

Then a mixture of 70 ml of dried benzene, 4.4 g ofN'-2-(5-hexylthio-1,3,4-thiadiazolyl)-N,N-dimethylformamidin and 2.7 gof diketene was refluxed for 6 hours. The reaction mixture wasconcentrated and the residue was purified by a silica gel columnchromatography using an ethyl acetate/n-hexane (1:3) mixture as aneluent. The eluent was distilled off, and thus 1.8 g of6-acetyl-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. Yield 36%.

PREPARATION EXAMPLE 21

Synthesis of6-cyano-2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

Eight (8) grams of 2-amino-5-heptylthio-1,3,4-thiadiazole, 3 g of ethyl3-ethoxy-2-propenoate, 10 g of polyphosphoric acid and 10 ml of xylenewere mixed, and the mixture was vigorously agitated at 125° C. for 30minutes.

After the reaction was finished, the reaction mixture was extracted withwater and toluene. The organic layer was washed with a sodium hydrogencarbonate aqueous solution and then with water. The solvent wasdistilled ethanol mixture and thus 7.4 g of2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was obtained.Yield 75%.

In 50 ml of acetic acid, 7.4 g of2-heptylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one and 5.3 g ofzinc chloride were dissolved. Six point three (6.3) grams of iodinemonochloride was added to the solution, and the mixture was stirred at70°˜80° C. for 1 hour.

After the reaction was finished, water and a salt water were added, andthe deposited crystals were collected by filtration. The collectedcrystals were washed with water and isopropyl ether, and thus 7.7 g of2-heptylthio-6-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. Yield 72%.

In 70 ml of dimethylformamide, 7.7 g of2-heptylthio-6-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved, and 3.4 g of cuprous cyanide, 1.8 g of sodium cyanide wereadded to the solution. The mixture was stirred at 130° C. for 3 hours.

After the reaction was finished, the reaction mixture was poured intowater. Toluene was added to the mixture and the mixture was stirredwell. The insoluble materials were collected by filtration with afiltration aid. The organic layer was washed with water and dried overanhydrous magnesium sulfate. The solvent was distilled off, and theremaining crude crystals were recrystallized from ethanol. Thus 2.1 g of2-heptylthio-6-cyano-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasobtained. Yield 37%.

PREPARATION EXAMPLE 22 Synthesis of2-hexylthio-7-cyano-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one(intermediate)

In 100 ml of dimethylformamide, 6 g of2-hexylthio-7-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one wasdissolved. To this solution, 1.77 g of copper cyanide and 0.97 g ofsodium cyanide were added and the solution was stirred at 100° C. for 1hour. After the reaction mixture was cooled to room temperature, it wasextracted with chloroform and water. The organic layer was washed withwater and dried over anhydrous sodium sulfate. Florisil® was added tothe organic layer and it was shaken. The solvent was distilled off, and2.3 g of 7-cyano-2-hexylthio-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-onewas obtained. Yield 51%.

FORMULATION EXAMPLE 1 Dust preparation

Two (2) % of Compound 1, 5% of diatomaceous earth and 93% of clay werehomogeneously mixed and ground to give a dust preparation.

FORMULATION EXAMPLE 2 Water-dispersible preparation

Fifty (50) % of Compound 2, 45% of diatomaceous earth, 2% of sodiumdinaphthylmethanesulfonate and 3% of sodium lignosulfonate werehomogeneously mixed and ground to give a water-dispersible preparation.

FORMULATION EXAMPLE 3 Emulsion preparation

Thirty (30) % of Compound 33, 20% of cyclohexanone, 11% ofpolyoxyethylenealkylaryl ether, 4% of calcium alkylbenzenesulfonate and35% of methylnaphthalene were homogeneously mixed and emulsified.

FORMULATION EXAMPLE 4 Granular preparation

Five (5) % of Compound 40, 2% of sodium salt of lauryl alcohol sulfateester, 5% of sodium lignosulfonate, 2% of carboxymethylcellulose and 86%of clay were homogeneously mixed and ground. To this mixture, 20% ofwater was added, and the mixture was made into granules of 14˜32 mesh bymeans of an extrusion granulator. The granules were dried and finishedas a granular preparation.

Now the fungicidal activity of the compounds of the present inventionwill be explained by way of test examples.

TEST 1 Protective Effect on Alternaria sooty spot of Chinese mustard(Brassica rapa var. pervidis)

Seeds of Chinese mustard were sown in 9 cm×9 cm plastic pots, 12 seedseach in a pot, and grown for 7 days in a greenhouse to the cotiledonousstage. Onto the grown seedlings a water-dispersible preparation preparedin accordance with the above Formulation Example 2, which was dilutedwith water to 50 ppm, was sprayed at a rate of 10 ml per pot. After thesprayed preparation was air-dried, the plants were inoculated with asuspension of spores of the pathogenic fungus of Alternaria sooty spotdisease (Alternaria brassicicola) by spraying and the pots were kept ina moist chamber at 30° C. After 3 days, number of lesions was countedand average numbers per leaf were recorded. The control activity wascalculated in accordance with the following definition. ##EQU1##

The results are shown in Table 2.

                  TABLE 2                                                         ______________________________________                                        Compound Tested                                                                              Control Activity                                               ______________________________________                                         1             63.9                                                            2             72.7                                                            3             96.2                                                            5             72.1                                                            6             97.5                                                            7             77.8                                                            8             86.1                                                           10             69.6                                                           13             72.7                                                           14             100                                                            16             77.2                                                           18             97.2                                                           19             82.3                                                           22             85.4                                                           23             72.7                                                           24             92.4                                                           25             100                                                            26             99.4                                                           27             76.6                                                           31             69.2                                                           34             89.3                                                           35             75.3                                                           37             96.2                                                           38             63.2                                                           40             93.7                                                           Captan*        51.2                                                           Untreated      0                                                              ______________________________________                                    

TEST 2 Control of apple Alternaria leaf spot

Young twigs with 6˜7 leaves detached from an apple tree (variety: Indo)were put in a glass cylinder. A water-dispersible preparation preparedin accordance with the above Formulation Example 2 was diluted to 1500ppm with water and sprayed thereonto. After air-dried, the plants wereinoculated with a suspension of spores of the pathogenic fungus ofAlternaria leaf spot (Alternaria mali) by spraying, and were kept in amoist chamber at 28° C. After 4 days, the damage index was worked out inaccordance with the following standard and the control activity wascalculated.

    ______________________________________                                         ##STR139##                                                                   N     is the total number of the examined leaves.                             n.sub.1                                                                             is the number of the affected leaves                                          on which area of lesions is less than 5%                                n.sub.2                                                                             is the number of the affected leaves                                          on which area of lesions is less than 5˜10%                       n.sub.3                                                                             is the number of the affected leaves                                          on which area of lesions is less than 11˜25%                      n.sub.4                                                                             is the number of the affected leaves                                          on which area of lesions is less than 26˜50%                      n.sub.5                                                                             is the number of the affected leaves                                          on which area of lesions is less than more than 51%                     n.sub.0                                                                             represents no affection                                                  ##STR140##                                                                   ______________________________________                                    

The results are shown in Table 3.

                  TABLE 3                                                         ______________________________________                                        Compound Tested                                                                              Control Activity                                               ______________________________________                                         1             96.0                                                            2             100                                                            10             97.2                                                           13             94.3                                                           14             82.9                                                           34             97.2                                                           35             100                                                            untreated      0                                                              ______________________________________                                    

TEST 3 Prevention of cucumber gray mold

Seeds of cucumber (variety: Sagami-hanjiro) were sown in 9 cm×9 cmsquare plastic pots, 12 seeds each in a pot, and grown in a greenhousefor 7 days. Onto the young seedlings, which have grown to thecotyledonous stage, a water-dispersible preparation prepared inaccordance with the above Formulation Example 2, which was diluted tothe active ingredient concentration of 500 ppm with water, was sprayedat a rate of 10 ml per pot. After the sprayed preparation was air-dried,the plants were inoculated with a homogenized hyphal suspension ofliquid culture of cucumber gray mold fungus (Botrytis cinearea) byspraying, and the pots were kept in a moist chamber at 20°˜23° C. Afterfour days, conditions of the affection were checked with respect to allthe pots.

    ______________________________________                                        Index of Affection                                                            ______________________________________                                               0: No affection                                                               1: Affected area is less than 25%                                             2: Affected area is 26˜50%                                              3: Affected area is 51˜75%                                              4: Affected area is more than 75%                                      ______________________________________                                    

The results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                               Compound                                                                              Index of                                                              Tested  Affection                                                      ______________________________________                                                1      0                                                                      3      1                                                                      5      0                                                                      7      1                                                                      8      1                                                                      9      0                                                                     10      0                                                                     13      0                                                                     14      0                                                                     18      0                                                                     19      1                                                                     20      0                                                                     22      0                                                                     23      0                                                                     24      0                                                                     25      0                                                                     26      0                                                                     27      0                                                                     28      0                                                                     29      1                                                                     30      0                                                                     31      0                                                                     32      0                                                                     33      0                                                                     34      0                                                                     35      0                                                                     37      0                                                                     40      0                                                                     41      0                                                                     42      0                                                                     43      0                                                                     44      0                                                                     45      0                                                                     46      0                                                                     47      1                                                                     48      0                                                                     49      0                                                                     50      0                                                                     51      0                                                                     52      0                                                                     53      0                                                                     54      0                                                                     55      1                                                                     56      0                                                                     57      0                                                                     58      0                                                                     59      0                                                                     60      0                                                                     61      1                                                                     62      0                                                                     63      0                                                                     64      0                                                                     65      1                                                                     66      0.5                                                                   68      0                                                                     69      0                                                                     70      0                                                                     71      0                                                                     72      0                                                                     73      0                                                                     75      1                                                                     76      0                                                                     77      1                                                                     78      0                                                                     79      0                                                                     80      0                                                                     81      0                                                                     82      1                                                                     84      0                                                                     85      2                                                                     86      1                                                                     87      1                                                                     88      0                                                                     89      0                                                                     90      1                                                                     91      0                                                                     92      0                                                                     93      0                                                                     94      0                                                                     95      0                                                                     96      1                                                                     97      1                                                                     98      2                                                                     99      2                                                                     100     0                                                                     101     1                                                                     102     0                                                                     103     0                                                                     104     0                                                                     105     0                                                                     106     1                                                                     107     0                                                                     108     0                                                                     109     0                                                                     110     0                                                                     112     1                                                                     113     0                                                                     114     0                                                                     115     0                                                                     116     0                                                                     117     1                                                                     118     1                                                                     119     1                                                                     120     0                                                                     121     0                                                                     122     0                                                                     125     0                                                                     126     0                                                                     127     0                                                                     128     0                                                                     130     0                                                                     131     0                                                                     132     0                                                                     153     0                                                                     164     0                                                              ______________________________________                                    

The other compounds were also effective on cucumber gray mold.

TEST 4 Protective effect on rice blast

Each 20 seeds of rice (variety: Aichiasahi) were sown in flowerpots 9 cmin diameter of white porcelain, and grown in a greenhouse for 3˜4 weeks.Onto the young seedlings, at the 4 leaf stage, a water-dispersiblepreparation prepared in accordance with the above Formulation Example 2,which was diluted with water to the active ingredient concentration of500 ppm was sprayed at a rate of 10 ml per pot. After the sprayedpreparation was air-dried, the seedlings were inoculated spores of thepathogenic fungus of rice blast (Pyricularia oryzae) suspended in waterby spraying in a moist chamber at 25° C. The disease development wasallowed in the greenhouse for 5 days. The numbers of lesions werecounted and the control activity was calculated. ##EQU2##

The results are shown in Table 5.

                  TABLE 5                                                         ______________________________________                                               Compound                                                                              Control                                                               Tested  Activity                                                       ______________________________________                                               42      79.3                                                                  43      84.4                                                                  44      86.0                                                                  45      93.3                                                                  46      92.1                                                                  47      79.1                                                                  48      98.0                                                                  49      97.2                                                                  50      89.4                                                                  51      70.7                                                                  52      98.3                                                                  53      63.4                                                                  54      75.9                                                                  55      93.4                                                                  57      83.0                                                                  58      89.7                                                                  59      93.9                                                                  60      92.1                                                                  61      75.3                                                                  62      95.3                                                                  63      76.5                                                                  64      66.0                                                                  65      80.4                                                                  66      87.0                                                                  67      83.3                                                                  68      96.3                                                                  70      85.0                                                                  71      91.3                                                                  72      90.5                                                                  73      85.5                                                                  75      81.0                                                                  76      85.4                                                                  77      92.4                                                                  78      79.7                                                                  79      90.3                                                                  80      88.2                                                                  81      89.0                                                                  82      75.4                                                                  83      100.0                                                                 84      64.4                                                                  85      86.8                                                                  86      91.3                                                                  87      79.3                                                                  88      81.3                                                                  89      71.8                                                                  90      78.1                                                                  91      88.5                                                                  92      75.4                                                                  93      74.1                                                                  94      96.3                                                                  95      88.7                                                                  97      92.5                                                                  98      88.1                                                                  99      77.7                                                                  100     80.4                                                                  101     75.9                                                                  102     81.2                                                                  103     78.6                                                                  104     89.8                                                                  105     94.6                                                                  106     91.7                                                                  107     96.7                                                                  108     65.8                                                                  109     77.8                                                                  110     84.8                                                                  111     79.1                                                                  113     69.4                                                                  114     83.7                                                                  115     96.3                                                                  116     85.6                                                                  117     81.4                                                                  118     100.0                                                                 119     94.6                                                                  120     69.9                                                                  121     86.9                                                                  122     86.4                                                                  125     74.7                                                                  126     86.3                                                                  127     73.3                                                                  128     68.7                                                                  129     71.2                                                                  130     93.6                                                                  131     93.6                                                                  132     99.2                                                                  133     66.3                                                                  134     67.8                                                                  135     83.2                                                                  136     89.3                                                                  153     96.2                                                                  162     79.3                                                                  163     85.5                                                                  164     97.4                                                                  167     94.3                                                                  168     82.3                                                                  169     97.2                                                                  170     86.2                                                                  171     79.4                                                                  172     96.9                                                                  173     77.8                                                                  175     98.5                                                           ______________________________________                                    

The other compounds were also effective on rice blast.

TEST 5 Control of tomato late blight (Field test)

Tomato seedlings (variety: Ohgata-Fukuju) were transplated on 20th Aug.,1986. Plants which had grown to have 12˜13 leaves were used for thetest.

Each 5 plants were designated 1 plot and 3 plots underwent the sametreatment.

Application of the fungicide was carried out three times on 30th Sept.,7th and 14th Oct. The fungicide was sprayed at a rate of 2 liters pereach 3 plots.

Disease severity was examined on 21st Oct. with respect to the fourth toninth leaves. The degree of damage and control activity were calculatedin accordance with the following results.

    ______________________________________                                        Rating                                                                        Index     Proportion of affected area                                         ______________________________________                                        0         0                                                                   1         less than 1/3                                                       2         1/3 to 2/3                                                          3         more than 2/3                                                        ##STR141##                                                                    ##STR142##                                                                   ______________________________________                                    

Results are shown in Table 6.

                  TABLE 6                                                         ______________________________________                                        Compound             Degree of  Control                                       Tested  Conc. (ppm)  Damage (%) Activity (%)                                  ______________________________________                                         91     500          3.2        96.7                                           94     "            8.3        91.5                                          103     "            4.8        95.1                                          104     "            0.8        99.2                                          113     "            6.5        93.4                                          115     "            1.2        98.8                                          TPN*    1000         26.2       73.3                                          Untreated                       0                                             ______________________________________                                         *TPN (tetrachloroisophthalnitrile)                                       

We claim:
 1. A method of protecting plants against agriculture orhorticultural fungi, which comprises applying to said plants afungicidally effective amount of a5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one compound represented by theformula (I) ##STR143## wherein X stands for a hydrogen atom, a halogenatom, a linear or branched lower alkyl group, a lower alkoxy group, alower acyl group, a trihalo-lower-alkoxy group, a lower alkynyl group, aphenyl group, a cyano group, a phenoxy group or a nitro group;Y standsfor a hydrogen atom, a halogen atom, a linear or branched lower alkylgroup, a halo-lower-alkyl group, a lower alkoxy group, a lower alkynylgroup, a phenyl-lower-alkynyl group, a lower-alkyl-amino group, or acyano group; and R stands for a linear or branched alkyl group, acyclohexyl-lower-alkyl group, a lower alkenyl group, a cyclohexyl group,a phenoxy-lower-alkyl group, a halo-alkyl group, a halo-alkenyl group, alower-alkoxycarbonyl-lower-alkyl group, atri-lower-alkyl-silyl-lower-alkyl group, a phenyl-lower-alkyl group, analkoxy-lower-alkyl group, a phenyl group which may be substituted withone or more halogen atoms, lower alkyl groups or nitro groups or loweralkoxy groups; a group represented by the formula ##STR144## wherein Zstands for a halogen atom, a lower alkyl group, a lower alkoxy group, atri-halo-lower-alkyl group or a nitro group, and n is an integer of 1 or2, and where Z is nitro, n is 1, wherein the two substituents may be thesame or different; with a proviso that when X is a hydrogen atom, ahalogen atom, a nitro group, or an alkyl group and Y is an alkyl group,R is not an alkyl group nor a phenyl-lower-alkyl group.
 2. The method ofclaim 1, wherein X stands for a hydrogen atom, a halogen atom, alower-alkyl group, a C₁₋₃ -alkoxy group, an ethynyl group, an acetylgroup, a trifluoroethoxy group, a phenyl group, a phenoxy group, a nitrogroup or a cyano group; Y stands for a hydrogen atom, a halogen atom, alower-alkyl group, a chloromethyl group, a lower-alkoxy group, alower-alkynyl group, a phenylethynyl group, a C₂₋₃ -alkylamino group ora cyano group; and R stands for a C₁₋₉ -alkyl group, a cyclohexylmethylgroup, an allyl group, a cyclohexyl group, a phenoxyalkyl group, ahaloalkyl group, a dichloroalkenyl group, an ethoxycarbonylbutyl group,an alkoxyalkyl group, a phenyl-lower-alkyl group, atrimethylsilyl-propyl group, a phenyl group which may be substitutedwith a halogen atom, a lower-alkyl group, a lower alkynyl group, a nitrogroup, a group represented by the formula ##STR145## wherein Z standsfor a halogen atom, a C₁₋₄ -alkyl group, a C₁₋₃ -alkoxy group, atrifluoromethyl or a nitro group.
 3. The method of claim 2, wherein Xstands for a hydrogen atom, a halogen atom, a lower alkyl group, a loweralkoxy group, an ethynyl group, an acetyl group or a cyano group; Ystands for a hydrogen atom, a halogen atom, a lower alkyl group, a loweralkoxy group, a lower alkynyl group or a cyano group; and R stands for aC₁₋₉ -alkyl group, a trimethylsilylpropyl group, a phenethyl group, aphenyl group, a phenyl or phenethyl group which may be substituted withone or two chlorine or fluorine atoms or lower alkyl groups or a benzylgroup having the formula ##STR146## wherein Z_(n) is one or two halogenatoms or one or two lower alkyl groups.
 4. The method of claim 3,wherein X stands for a hydrogen atom, a halogen atom, a methyl group, amethoxy group, an ethynyl group, a cyano group, an acetyl group; Ystands for a hydrogen group, a halogen atom, an ethynyl group, apropynyl group or a cyano group; R stands for a C₄₋₉ -alkyl group, atrimethylsilylpropyl group, a phenyl group, which may be substitutedwith a halogen atom or a methyl group, or a benzyl group having theformula ##STR147## wherein Z_(n) is one or two halogen atoms or one ortwo methyl groups.
 5. The method of claim 1, wherein said compound is2-hexanesulfonyl-6-chloro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one. 6.The method of claim 1, wherein said compound is2-hexanesulfonyl-7-(1-propynyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one7. The method of claim 1, wherein said compound is2-hexanesulfonyl-7-ethynyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.8. The method of claim 1, wherein said compound is2-hexanesulfonyl-6-chloro-7-fluoro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.9. The method of claim 1, wherein said compound is2-hexanesulfonyl-6-chloro-7-ethynyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.10. The method of claim 1, wherein said compound is2-octanesulfonyl-6-methoxy-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.11. The method of claim 1, wherein said compound is2-heptanesulfonyl-6-cyano-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.12. The method of claim 1, wherein said compound is2-heptanesulfonyl-6-acetyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.13. The method of claim 1, wherein said compound is2-pentanesulfonyl-6-chloro-7-fluoro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one.